Inclusion Criteria:
1. Participants must be \>18 years old at time of diagnosis
2. Histologically confirmed adenocarcinoma of the rectum from biopsy, defined as adenocarcinoma \<15 cm from the anal verge
3. Clinical staging including T3N0 tumors, or T1-3 with N1-2a disease
4. Patients with lower rectal cancer deemed by surgery to not be candidates for sphincter sparing surgery are eligible to participate
5. There must be no evidence of metastatic disease any time prior to initiation of study
6. Rectal tumors must be determined as likely requiring total mesorectal excision (TME)
7. Participant must be treatment naïve for rectal cancer, with no prior radiation chemotherapy, radiation, or surgery for specific rectal cancer
8. No history of prior pelvic radiation
9. No prior administration of platinum agents
10. No active infections requiring intravenous antibiotics
11. No additional active malignancy
12. No prior treatment of any malignancy within the past 3 years
13. Baseline lab work must meet the following parameters:
1. Absolute neutrophil count (ANC)\>1500/mm3
2. Platelet count\>100,000/mm3
3. Hemoglobin\>8.0 g/dL
4. Total bilirubin and creatinine \< 1.5x upper limit of normal (ULN)
5. AST and ALT \< 3x ULN
14. Women of childbearing potential (WCBP) will be defined as those biologically capable of becoming pregnant. WCBP must be negative for pregnancy testing (urine or blood) and agree to use effective contraception. Viable contraception should be used after trial screening, before initiation of chemotherapy, and throughout the duration of active treatment in the study.
15. Participants must be read and explained the purposes of the study, and sign a statement of informed consent prior to participation. Those who do not read or understand English are eligible and may be consented according to institutional federal regulations.
Exclusion Criteria:
1. Recurrent or refractory rectal adenocarcinoma
2. T1N0, T2N0, T4a, T4b, or N2b tumors
3. Any evidence of metastatic disease
4. Primary unresectable rectal cancer. A tumor will be considered unresectable when invading adjacent organs such that an en bloc resection cannot achieve negative margins
5. Patients with threatened margins, defined as tumor \<1 mm from circumferential resection margins or mesorectal fascia
6. Patients unable to undergo MRI imaging
7. Patient with a history of any arterial thrombotic event within the past 6 months. This includes angina, myocardial infarction, transient ischemic attack, or cerebral vascular accident.
8. Patients with history of venous thrombotic episodes such as deep vein thrombosis, pulmonary embolus occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Patients who are anticoagulated for atrial fibrillation or other conditions may participate only if on stable doses of anticoagulant therapy.
9. Patients with cardiovascular, hepatic, or renal systemic diseases that would preclude use of chemotherapy
10. Peripheral neuropathy\>grade 1 by Common Terminology Criteria for Adverse Events, or CTCAEa
11. The patient must not be on any clinical trials involving other experimental therapies before or during study treatment
12. Women who are currently pregnant or breast-feeding
13. Men and women expecting to father/conceive children
14. Patients with any other concord medical or psychiatric condition which were deemed inappropriate for entry into the study per the investigator.
15. History of other invasive malignancy within the past 3 years, except for adequately treated non-melanoma skin cancer, ductal carcinoma in situ, bladder carcinoma in situ or carcinoma in situ of the cervix.
aCTCAE version 5.0 from Department of Health and Human Services
